3.5 | Case Study: E194G of CASQ
The calsequestrin (CASQ) is the Ca2+ buffering
protein, which could store large amounts of Ca2+ in
the cardiac and skeletal muscles. Ca2+ is an essential
molecular that could regulate diverse cellular processes, such as gene
transcription, cell proliferation, or migration
(Kim, Tam, Siems, & Kang, 2005;
MacLennan, Abu-Abed, & Kang, 2002;
Manno et al., 2017). Though most
researches of CASQ are focus on the cardiac muscle, CASQ in the
Ca2+ signal pathway is also vital in cancer research
(Terentyev et al., 2003). It is reported
that the Ca2+ signaling pathway is highly correlated
to tumor growth or metastatic (Stewart,
Yapa, & Monteith, 2015), and E194G of CASQ has been found in
glioblastoma patients (Parsons et al.,
2008). In CASQ, T189, E194, and D196 would form a pack harboring
Ca2+ (Sanchez, Lewis,
Danna, & Kang, 2012). Hence, this substitution, E194G, would lose it
functional and destroy the Ca2+ binding (Figure 5).
Although no micro-environment descriptor has a significant difference at
95% confidence interval between the distribution of cancer-related and
neutral SAVs in GLU altered to GLY sub-group, several relevant
descriptors are found in the case of E194G in CASQ. E194 has higher WCN
values of oxygen in a single SAV chain and atoms in other molecular due
to CASQ is a GLU and ASP rich and Ca2+ buffering
protein (Figure 6 a, b). Furthermore, for the micro-environment around
E194, higher WCN values are found than the third quartile of
cancer-related SAVs in H -polar (RKEDQN), V -medium
(NVEQIL), Z -low polarizability(GASDT), P -high polarity
(HQRKNED), F -acidic (DE), and E -acidic (DE) descriptors
and lower than the first quartile in E -sulfur-containing (CM).
The boxplot of the micro-environment descriptors in GLU altered to GLY
sub-group is shown in figure 6.